Continuation of this project in FY-90 has included completion of a study of the interaction of age and transdermal estradiol replacement at 3 different doses in 28 postmenopausal women, investigating effects of estrogen with and without progestogen on basal growth hormone (GH) and IGF-1, GH responses to GHRH, as well as calciotropic and gonadotropic hormone regulation. We found: (1) older women remain responsive to the bone- conserving action of estrogen; and (2)estrogens' action to preserve bone mass appears to be independent of any modulation of GH, IGF-1, or calcitonin secretion. A study to quantitate the effects of aging on the regulation of the hypothalamic-pituitary-adrenal axis has also been completed in 11 young and 11 older men, using overnight monitoring of pituitary-adrenal function with 12 hours of every 10-minute blood samples followed by CRH stimulation tests under basal conditions and then 4 hours of every 10-minute blood sampling followed by CRH stimulation tests repeated at weekly intervals during ACTH suppression with each of 3 doses of dexamethasone. Results showed that both spontaneous and CRH-stimulated secretion of ACTH and cortisol were unchanged with age and responded similarly to suppression with graded doses of dexamethasone. These findings provide strong evidence against the hypothesis that an age-related loss of sensitivity of the hypothalamic-pituitary-adrenal axis to negative feedback by glueocorticoids leads to glucocorticoid excess and resultant changes in body composition and metabolism. A new study using 24 hr. monitoring of spontaneous pulsatile GH secretion, acute GH response to iv GHRH, and plasma IGF-I measurements, all done before after two weeks of chronic GHRH injections repeated at 2 different doses, has been initiated in order to investigate the relationship of GH deficiency to aging and to test the effectiveness of possible interventions for raising GH and IGF-I secretion in older people.